In U.S. Pat. No. 5,256,294, titled "TANGENTIAL FLOW FILTRATION PROCESS AND APPARATUS," by Robert D. van Reis, et al., Oct. 26, 1993, and U.S. Pat. No. 5,490,937, titled "TANGENTIAL FLOW FILTRATION PROCESS AND APPARATUS," by Robert D. van Reis, et al., Feb. 13, 1996, a system for concentrating and washing proteins is described that employs cassette-type (similar to plate-and-frame) ultrafiltration membranes of various decreasing sizes for separating protein mixtures while maintaining a flux ranging from 5% to 100% of transition flux. Transmembrane pressure is maintained substantially consistent along the length of the membrane at a level no greater than the transition flux. A backpressure control valve is used on the permeate flow such that a constant pump speed is maintained while the permeate flow can dictate a constant concentration of material to be retained at the wall of the membrane. In this way, a vast reduction of the concentration polarization layer allows for more consistent purification of the proteins. The disadvantages in these methods are that they are not proven for spiral wound confirmation, an additional control valve is required for the permeate and the pump speed and pressure on the modules are not reduced.
In U.S. Pat. No. 5,164,092, titled "2-STAGE ULTRAFILTRATION PROCESS FOR PHOTOGRAPHIC EMULSIONS," by William D. Munch, Nov. 17, 1992, a two-stage system for concentrating and washing photographic emulsions to high viscosities is described that employs spiral wound ultrafiltration as the first stage. Plate-and-frame (of which cassettes are a variety) ultrafiltration is the second stage. Although the goal of further concentrating emulsions to appropriate curtain-coating levels achieved by the combination of the ultrafiltration module designs, first batch yield losses and yield variability was not addressed. These are important due to the cost of lost product in lost yield which, in this case, occurs only in the first batch after a chemical cleaning. Furthermore, since it only occurs on a first batch after a chemical cleaning, the yield will be lower for that batch than for the one to seven additional batches that follow before the next chemical cleaning. Since up to 50 additional chemicals can be added in the downstream batch process, the variability in the yield can lead to manually having to cut the amounts of those 50 chemicals depending on the yield. If the yield were dependably high, computer generated amounts of chemicals could be added in the downstream batch process at a constant amount for each batch. Without a dependably high yield it is necessary to manually adjust depending on the yield variability. These issues were not addressed since the traditional process control strategy was used. This process employs the much-used process control strategy of a positive displacement pump operating at constant, relatively high speed. The pump speed control is nested with a feed flow backpressure control valve. Together, the pump speed, which is approximately 300 rpm, and feed backpressure control in the process result in a relatively high feed inlet pressure setpoint. In this scheme, transmembrane pressure for the filtration is maintained along the membrane substantially higher than the transmembrane pressure at the transition point of the filtration.
The resulting concentration polarization layer build up prevents concentration to levels required in certain applications. Thus, the additional concentration apparatus, i.e. the plate-and-frame UF module is required to achieve the target concentrations with the addition of considerable process time due to the severely reduced surface area of the plate-and-frame arrangement.